Featured Research

from universities, journals, and other organizations

Researchers solve a molecular mystery in muscle

Date:

March 15, 2010

Source:

University of Michigan

Summary:

Despite widespread interest in insulin-like growth factors, key details about how these potent molecules work on muscle cells have been lacking. Researchers have now cleared up a longstanding mystery about the workings of IGFs. The team's findings could lead to new treatments for muscle-wasting diseases and new ways of preventing the muscle loss that accompanies aging.

Share This

The muscle-building abilities of hormones known as insulin-like growth factors (IGFs) are legendary. Just do an online search and you'll find not only scientific papers discussing the effects of IGFs on the cells that give rise to muscle tissue, but also scores of ads touting the purported benefits of IGF supplements for bodybuilding.

Related Articles

But in spite of widespread interest in these potent molecules, key details about how IGFs work on muscle cells have been lacking.

A research by a team led by University of Michigan molecular biologist Cunming Duan has cleared up a longstanding mystery about the workings of IGFs. The team's findings, scheduled to be published online in the Proceedings of the National Academy of Sciences, could lead to new treatments for muscle-wasting diseases and new ways of preventing the muscle loss that accompanies aging.

And because IGFs also are implicated in the growth and spread of malignant tumors, the new insights may have implications in cancer biology.

Like other peptide and protein hormones, IGFs work by binding to receptors on the cells they target. The binding then sets off a cascade of reactions that ultimately direct the cell to do something. You might think that a given hormone, binding to a particular receptor, would always elicit the same response from the cell, but that's not what happens in the case of IGF and myoblasts (immature cells that develop into muscle tissue).

During muscle formation, the binding of IGF to its receptor can prompt either of two very different responses in myoblasts, said Duan, a professor in the Department of Molecular, Cellular and Developmental Biology. Some of the cells are stimulated to divide, while others interpret the very same signal as an order to differentiate (become specialized).

"These are opposite and mutually exclusive cellular events -- once a muscle cell divides, it can't differentiate, and once it differentiates, it can never divide again," Duan said. How activation of the same receptor by the same hormone can elicit two such distinctly different responses has been one of the most puzzling questions about IGF, but Duan and colleagues have found the answer.

"The myoblasts' response is controlled by oxygen availability," said Duan. When oxygen levels are normal, IGF promotes muscle cell differentiation; when oxygen levels are below normal, IGF promotes muscle cell division. Teasing out the molecular details, the researchers discovered that low oxygen activates an intermediary called the HIF-1 complex, which reprograms the cascade of steps that ultimately controls the cell's response.

The findings not only reveal how muscle cells respond to varying oxygen levels during normal development, but also have implications for human disease, Duan said. "For example, a major reason that muscle atrophy occurs as people get older is that the IGF signal gets weaker. If we can find a way to affect IGF signaling, we may be able to stop or reverse the loss." Although manipulating the oxygen levels in living cells could be difficult, it may be possible to manipulate HIF-1 in ways that would mimic changing oxygen levels.

The work also could help scientists better understand the processes involved in cancer progression and spread. It's known that IGF can promote tumor cell division and survival and also that oxygen levels are often lower in tumor tissue than in normal tissue. Finding the link between IGF activity and oxygen levels may lead to new strategies for cancer treatment.

Duan's coauthors on the paper are former graduate student Hongxia Ren, now a postdoctoral fellow at Columbia University, and Domenico Accili, professor of medicine at Columbia .

The research was funded by the National Institutes of Health, the National Science Foundation and the University of Michigan.

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015 — Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015 — No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015 — Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015 — Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015 — Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015 — Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Mar. 3, 2015 — Twice as many children born to mothers who took antibiotics during pregnancy were diagnosed with asthma by age 3 than children born to mothers who didn’t take prenatal antibiotics, a new study has ... full story

Mar. 3, 2015 — Pediatric otolaryngologists and surgeons are concerned with parents getting the wrong message regarding the safety/desirability of letting babies and young children eat peanuts to prevent them from ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) — After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015) — Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) — A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

Oct. 23, 2013 — A new study reveals that tumors release factors into the bloodstream that inhibit the repair of damaged muscle fibers, and that this contributes to muscle loss during cancer wasting. The condition, ... full story

Sep. 17, 2012 — Muscles have a pool of stem cells in special niches which provides a source for muscle growth and for the regeneration of injured muscles. Researchers have elucidated how these stem cells colonize ... full story

Feb. 29, 2012 — If you want big muscles without working out, there's hope. Scientists report a family of protein transcription factors, called "Forkhead (Fox0)," that plays a significant role in the ... full story

Jan. 3, 2012 — We take it for granted, but the fact that our muscles grow when we work them makes them rather unique. Now, researchers have identified a key ingredient needed for that bulking up to take place. A ... full story

Oct. 1, 2010 — Growth hormone has multiple effects on skeletal muscle, including promoting growth and regeneration. It is not clear, however, which effects are direct and which are mediated via induction of the ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.